102 articles - From Friday May 13 2022 to Friday May 20 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
meta-analyses and systematic reviews
| Thromb Haemost |
Clopidogrel monotherapy versus Aspirin monotherapy in patients with established cardiovascular disease: systematic review and meta-analysis. In patients with established cardiovascular disease, Clopidogrel was associated with a 17% relative-risk reduction for non-fatal MI, borderline decreased risk for MACE and similar risk for all-cause mortality, stroke and major bleeding compared to Aspirin. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
American Journal of Hematology - Test of the Month "Optical Genome Mapping for Structural Variation Analysis in Hematologic Malignancies". Parallel studies of OGM versus standard of care testing have demonstrated it can detect and resolve more abnormalities than karyotyping or FISH. However, like many molecular tests that normalize copy number it can have difficulty with non-diploid karyotypes. This Test of the Month review will summarize how the technique works, review the strengths and weaknesses of OGM compared to standard of care techniques and illustrate how the technique is likely to change front line testing in many hematologic malignancies - including summarizing the clinical utility in Acute Myeloid Leukemia, Myelodysplastic syndromes and B-Cell Acute Lymphoblastic Leukemia. |
Combining CD34+ stem cell selection with prophylactic pathogen and leukemia directed T-cell immunotherapy to simultaneously reduce graft versus host disease, infection and leukemia recurrence after allogeneic stem cell transplant. Combining robust donor T-cell depletion with directed T-cell adoptive immunotherapy targeting infectious and malignant antigens permits independent modulation of GVHD, infection and disease recurrence. The combination may separate GVHD from the graft versus tumor effect, accelerate immune reconstitution and improve transplant tolerability. |
Long-term outcomes of patients with conjunctival extranodal marginal zone lymphoma. CR following frontline therapy was associated with longer PFS (HR=0.13, 95%CI 0.04-0.45; p=0.001), but not OS. Using the Fine and Gray regression model with death without relapse/progression as a competing risk, RT and CR after frontline therapy were associated with lower risk of relapse (SHR=0.34, 95%CI 0.12-0.96 p=0.041 and SHR=0.11, 95%CI 0.03-0.36; p<0.001, respectively). Patients with PCEMZL treated with frontline RT exhibit excellent long-term survival, and the MALT-IPI score appropriately identifies patients at risk for treatment failure. |
Multiple Myeloma: 2022 update on Diagnosis, Risk-stratification and Management. Patients who not candidates for transplant are treated with VRd for approximately 8-12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression. Maintenance therapy Standard risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high-risk myeloma. Management of relapsed disease A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse. |
Outcomes following venetoclax-based treatment in therapy-related myeloid neoplasms. In a propensity matched analysis, the use of venetoclax-based regimen as the first-line therapy was associated with a superior survival compared to hypomethylating agent (HMA)-based first-line therapy (9.4 vs 6.1 months, P=0.01). We conclude that the upfront use of venetoclax with HMA improved survival, though PFS and OS remain poor. As the phenotype at diagnosis or the percent blasts did not predict outcomes, venetoclax should be studied in al t-MN phenotypes. |
TP53-altered CLL Treated with Firstline Bruton's Tyrosine Kinase Inhibitor-based Therapy: A Retrospective Analysis. No baseline characteristics including IGHV mutation status and number of TP53 alterations were associated with significant differences in PFS or OS, though a trend towards shorter PFS with increasing karyotypic complexity (hazard ratio 1.08, p=0.066) was observed. Del(17p) was identified in <25% of cells in 26/104 (25%) of patients, and 28/101 (28%) of TP53-m were low-burden with a VAF of <10%; outcomes of these patients were similar to those with high-burden lesions. This study suggests that low-burden TP53 alterations should not be ignored when assessing genomic risk in CLL in the era of targeted therapy. |
Trajectories of quality of life recovery and symptom burden after autologous hematopoietic cell transplantation in multiple myeloma. Low symptom burden was reported by 27% of patients at baseline, 38% at 1-year, and 32% at 4 |
Venetoclax Combined with FLAG-IDA Induction and Consolidation in Newly Diagnosed Acute Myeloid Leukemia. FLAG-IDA+VEN is an active regimen in ND-AML capable of producing high MRD-negative remission rates and enabling transition to alloHSCT when appropriate in most patients. Toxicities were as expected with IC and were manageable. Estimated 24-month survival appears favorable compared to historical IC benchmarks. |
| Ann Oncol |
Risk-adapted modulation through de-intensification of cancer treatments: an ESMO classification. ESMO classification for the risk-guided intensity modulation of cancer treatments provides a set of evidence-based criteria to categorise biomarkers deemed to inform de-intensification of cancer treatments, in risk-defined patients. The classification aims at harmonising definitions on this matter, therefore offering a common language for al the relevant stakeholders, including clinicians, patients, decision-makers, and for clinical trials. |
| Blood |
CAR T-cell Therapy in Highly-Aggressive B-Cell Lymphoma: Emerging Biological and Clinical Insights. Recent reports suggest that this is an effective strategy for high-grade B-cell. The biological underpinnings of these entities and how they overlap with each other and DLBCL continue to be areas of intense investigation. Therefore, as more experience with CAR T-cell approaches is examined, it is interesting to consider how both tumor-cell specific and microenvironment factors that define these highly aggressive subsets influence susceptibility to this approach. |
Cytosine Base Editing Enables Quadruple-Edited Allogeneic CAR-T Cells for T-ALL. We show that CBE, unlike CRISPR-Cas9, does not impact T-cell proliferation, lead to aberrant DNA damage response pathway activation or result in karyotypic abnormalities following multiplexed editing. We demonstrate 7CAR8 to be highly efficacious against T-cell acute lymphoblastic leukemia (T-ALL) using multiple in vitro and in vivo models. Thus, CBE is a promising technology for applications requiring multiplexed gene editing and can be used to manufacture quadruple-edited 7CAR8 cells with high potential for clinical translation for relapsed and refractory T-ALL. |
Daratumumab in first-line is cost-effective in transplant-eligible newly diagnosed myeloma patients. In the Japanese analysis, D-RVd showed higher QALYs (5.43 vs 5.18) and lower costs (¥ 64,479,793 vs 71,287,569) compared to RVd, and D-VTd showed higher QALYs (5.67 vs 5.42) and lower costs (¥ 43,600,310 vs \ 49,471,941) compared to VTd. Similarly, the US analysis demonstrated dominance of a strategy incorporating daratumumab in first-line treatment regimens. Given that overall costs are reduced and outcomes are improved when daratumumab is used as part of a first-line regimen, the economic analysis indicates that addition of daratumumab to first-line RVd and VTd regimens is a dominant strategy compared to reserving its use for the second-line setting. |
How We Approach Smoldering Multiple Myeloma. The current standard of care in smoldering multiple myeloma (SMM) is close surveillance, outside of clinical trials. Efforts are being made to understand the pathobiological process that leads to the progression of SMM to active multiple myeloma (MM). This review provides a critical description of the available data, including the risk factors and the risk models of progression, as well as the clinical trials that investigate interventions for this patient population. |
Monoclonal and oligoclonal anti-Platelet Factor 4 antibodies mediate VITT. Persistent platelet-activating antibodies were detected at 1.5 and 2.5 months after acute presentation in two patients tested. This study demonstrates that mono/oligoclonal anti-PF4 antibodies mediate VITT and are frequently persistent. As VITT antibody-mediated platelet activation is inhibited by heparin, additional studies to evaluate a potential role of heparin treatment in VITT may be warranted. |
MRD in multiple myeloma: does CR really matter? However, there are conflicting results between the achievement of complete remission and MRD negativity, because some patients with persistent M-protein have nonetheless undetectable MRD. We reviewed the frequency of this discordancy and the outcome of these patients. We spotlighted possible explanations and consequences of conflicting response criteria, and suggest that MRD should be assessed in patients achieving very good partial response or better in clinical trials. |
Patients with CLL have lower risk of death from COVID-19 in the omicron era. In a cohort of patients with CLL tested for severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) at hospital test sites in the time periods before and after dominance of the omicron variant, rates of hospitalizations and ICU-admissions declined significantly, whereas 30-day mortality remained as high as 23% in the period with dominance of the omicron sublineage BA.2 variant. However, for a larger population-based cohort of patients with CLL (including the hospital cohort), 30-day mortality was 2%. Thus, patients with CLL with close hospital contacts and in particular those above 70 years of age with one or more comorbidities should be considered for closer monitoring and pre-emptive antiviral therapy upon a positive SARS-CoV-2 test. |
Revisiting anemia in sickle cell disease and finding the balance with therapeutic approaches. However, although anemia is clearly associated with many detrimental outcomes, it may also have an advantage in SCD in lowering risks of potential viscosity-related complications. Until recently, clinical drug development for SCD has predominantly targeted a reduction in the frequency of vaso-occlusive crises as an endpoint, but increasingly, more attention is being directed toward addressing the contribution of chronic anemia to poor outcomes in SCD. This article aims to explore the complex pathophysiology and mechanisms of anemia in SCD, as well as the need to balance the benefits of raising hemoglobin levels with the potential risks of increasing blood viscosity, in the context of the current therapeutic landscape for anemia in SCD. |
ROR1 - An Orphan Becomes Apparent. Chronic lymphocytic leukemia (CLL) was the first malignancy found to have distinctive expression of ROR1, which can help distinguish leukemia cells from most non-cancer cells. Aside from its potential utility as a diagnostic marker or target for therapy, ROR1 also factors in the pathophysiology of CLL. Here we review the studies that have elucidated the expression, biology, and evolving strategies for targeting ROR1 that hold promise for improving the therapy of patients with CLL or other ROR1-expressing malignancies. |
THE ANTIBODY-DRUG CONJUGATE LONCASTUXIMAB TESIRINE FOR THE TREATMENT OF DIFFUSE LARGE B-CELL LYMPHOMA. Relapsed/refractory disease represents remains an unmet medical need, despite the introduction of novel cellular and targeted therapies. Loncastuximab tesirine is a CD19-targeting antibody-drug conjugate approved by the US Food and Drug Administration for relapsed DLBCL after two lines of systemic therapy based on a trial showing a 48.3% overall response rate. The spectrum of its clinical applications is expanding and is now being tested in other B-cell malignancies. |
Thrombolytic tPA-Induced Hemorrhagic Transformation of Ischemic Stroke is Mediated by PKCß phosphorylation of Occludin. Blocking occludin phosphorylation either by targeted expression of a non-phosphorylatable form of occludin (S490A) or by pharmacologic inhibition of PKCß, reduced MCAO-induced permeability and improved functional outcome. Further, inhibiting PKCß after MCAO prevented ICH associated with delayed thrombolysis. These results reveal that PKCß phosphorylation of occludin is a downstream mediator of tPA-induced cerebrovascular permeability and suggest that PKCb inhibitors could improve stroke outcome and prevent ICH associated with delayed thrombolysis, potentially extending the window for thrombolytic therapy in stroke. |
| Blood Adv |
A 3-decade multicenter European experience with cladribine as upfront treatment in 384 hairy cell leukemia patients. Median progression-free survival was 13 years and median disease-free survival was 11 years. Cladribine is effective as frontline treatment of HCL and may determine deep disease control in a significant proportion of cases, given that more than 50% of treated patients require no further therapy. Good quality responses may be maintained for more than 20 years in up to 35% of patients. |
Allelic Complexity of KMT2A Partial Tandem Duplications in Acute Myeloid Leukemia and Myelodysplastic Syndromes. High copy numbers indicating complexity were significantly enriched in AML versus MDS and correlated with higher RNA expression. Moreover, in serial samples, complexity was associated with relapse and secondary transformation. Taken together, we provide approaches to integrate quantitative and allelic assessment of KMT2A-PTDs into targeted DNA NGS and demonstrate that secondary genetic events occur in KMT2A-PTD by multiple mechanisms that may be linked to myeloid disease progression by driving increased expression from the affected allele. |
Depletion of CLL cells by venetoclax treatment reverses oxidative stress and impaired glycolysis in CD4 T cells. Analysis of CD4 T cells from CLL patients prior and after venetoclax + obinutuzumab treatment, which led to effective clearance of CLL in blood and bone marrow, revealed recovery of T-cell activation and restoration of the switch to glycolysis, as well as improved T-cell proliferation. Collectively these data demonstrate that CLL cells impose metabolic restrictions on CD4 T cells which lead to reduced CD4 T-cell functionality. This trial is registered in the Netherlands Trial Registry ID: NTR6043. |
Developmental cues license megakaryocyte priming in murine hematopoietic stem cells. Importantly, we identify LIN28B - known for its role in promoting fetal-like self-renewal, as an insulator against the establishment of a Mk biased HSC pool. LIN28B protein is developmentally silenced in the third week of life and its prolonged expression delays emergency platelet output in young adult mice. We propose that developmental regulation of Mk priming may represent a switch for HSCs to toggle between prioritizing self-renewal in the fetus and increased host protection in postnatal life. |
Fatal Thrombotic Microangiopathy Case following Adeno-Associated Viral SMN Gene Therapy. Other cases of TMA have recently been reported after onasemnogene abeparvovec, and after AAV9 minidystrophin therapy in the Duchenne muscular dystrophy. The risk-benefit ratio of this therapy must therefore be assessed. Early recognition of TMA and targeted immunotherapy are fundamental to ensure the safety of patients treated with AAV gene therapies. |
Fibrin protofibril packing and clot stability are enhanced by extended knob-hole interactions and catch-slip bonds. Clot viscoelastic analysis showed that only |
GPVI expression is linked to platelet size, age, and reactivity. We further detected a higher GPVI expression in platelets of patients with immune thrombocytopenia. Our findings show that high GPVI expression is a feature of highly reactive juvenile platelets, which are predominantly found among the large platelet population explaining the better performance of large platelets during thrombus formation. These data are important for studies of thrombus formation, platelet storage and ITP. |
Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. No thromboembolic events were reported, and iptacopan was well tolerated, with no severe or serious adverse events reported up until the data cutoff. In addition to the previously reported beneficial effect of iptacopan add-on therapy to eculizumab, this study showed that iptacopan monotherapy in treatment-naïve PNH patients resulted in normalization of hemolytic markers and rapid transfusion-free improvement of hemoglobin levels in most patients. Registered at as NCT03896152. |
Lifetime medical costs attributable to sickle cell disease among nonelderly individuals with commercial insurance. The corresponding OOP estimates were $42,395 (95%CI: $34,756, $50,033) for females and $45,091 (95% CI: $36,491, $53,691) for males. These represent a 907% and 285% increase in total medical and OOP costs over controls, respectively. Although limited to the commercially insured population, these results indicate that the direct economic burden of SCD is substantial and peaks at younger ages, suggesting the need for curative and new medical therapies. |
Long-term patient-reported neurocognitive outcomes in adult survivors of hematopoietic cell transplant. In multivariable regression analyses, impaired Neuro-QoL (T-score <40) was independently associated with hearing issues (OR 2.13, 95% CI 1.46-3.10) and sleep impairment (OR 4.41, 95% CI 2.80-6.94) among allogeneic survivors, with comparable associations in autologous survivors. Overall, long-term adult HCT survivors reported average cognitive quality of life compared with the general population. Subsets of survivors with hearing issues and sleep impairments were more likely to report lower quality of life and impaired neurocognitive function, which may facilitate targeted monitoring or interventions following HCT. |
Monocytosis and its association with clonal hematopoiesis in community-dwelling individuals. In conclusion, monocytosis and CH both occur at older age and do not necessarily reflect clonal monocytic proliferation. In a fraction of older subjects with monocytosis, CH might constitute early clonal dominance in developing malignant myelomonocytic disease. Mutational spectra deviating from age-related CH require attention. |
Real-World Treatment Patterns and Outcomes of Mantle Cell Lymphoma. BTK inhibitors were the most preferred agents in second or later lines of therapy (n=933, 57%), followed by bortezomib, lenalidomide, and venetoclax, respectively. Among patients treated with BTK inhibitors, the median real-world overall survival (rwOS) was 35 months (95%CI 27-50), 24 months (95%CI 22 - 30), and 18 months (95% CI 14 - 21), for first line, second line and for third or later line of therapy, respectively. Patients with deletion 17p/TP53 mutation and blastoid variant MCL had poor outcomes; however, BTK inhibitors appeared to mitigate the negative influence of del17p/TP53 mutated MCL with an HR of 1.17 (95%CI 0.88 - 1.55) on multivariable analysis. |
Real-World Use of Tisagenlecleucel in Infant Acute Lymphoblastic Leukemia. No neurotoxicity was reported. This is the largest report of tisagenlecleucel use in infant B-ALL and shows that this therapy is safe and can be effective in this population. Incorporating this novel immunotherapy into the treatment of infant B-ALL offers a promising therapy for a highly aggressive leukemia. |
Relative hypercoagulation induced by suppressed fibrinolysis after tisagenlecleucel infusion in malignant lymphoma. Moreover, this suppressed fibrinolysis induced relatively hypercoagulable state was gradually resolved after CRS remission with normalization of total PAI-1 to pre-infusion levels without any organ damage (mean values of soluble fibrin: 3.16 µg/mL at baseline, 8.04 on Day3, and 9.16 on Day13, p<0.01 and mean PAI-1: 25.1 ng/mL on Day13). In conclusion, a hypofibrinolytic and relatively hypercoagulable state concomitant with significant total PAI-1 elevation was observed at the onset of CRS even in DLBCL patients with mild CRS. Our results will facilitate understanding of CRS-related coagulopathy and they emphasize the importance of monitoring sequential coagulation/fibrinolysis parameters during CAR-T therapy. |
Safety and efficacy of a dose-dense short-term therapy in patients with MYC-translocated aggressive lymphoma. HIV seropositivity had not a detrimental effect on outcome. This retrospective study shows that CARMEN is a safe and active regimen both in HIV-negative and -positive patients with MYC-rearranged lymphomas. Encouraging survival figures, attained with a single dose of doxorubicin and cyclophosphamide, deserve further investigation in HGBCL and other aggressive lymphomas. |
The Potential Role of Protease Systems in Hemophilic Arthropathy. MMPs are also implicated in the pathology of osteoarthritis (OA) characterized by degradation of the cartilage matrix that precipitates joint damage and deformity. HA shares a number of overlapping pathological characteristics with RA and OA. Here we discuss how the plasminogen activation system and MMPs might exacerbate joint damage in HA, lending insight into novel possible therapeutic targets to reduce co-morbidity of haemophilia. |
Unmasking the suppressed immunopeptidome of EZH2 mutated diffuse large B-cell lymphomas with combination drug treatment. Overall, these treatments restored the diversity of the immunopeptidome to levels described in healthy B cells for 2 out of 3 cell lines and allowed the systematic search for new targets for immunotherapy. Consequently, we identified multiple MHC ligands from regulator of G protein signaling 13 (RGS13) and E2F transcription factor 8 (E2F8) on different MHC alleles, none of which have been described in healthy tissues and therefore represent tumor-specific MHC ligands, which are unmasked only after drug treatment. Overall, our results show that EZH2 inhibition in combination with decitabine and IFN- |
| Haematologica |
Assessment of functional shunting in patients with sickle cell disease. We included 28 children and 38 adults with SCD, and 10 healthy race-matched adult controls. VS, cerebral blood flow (CBF), velocity in the brain feeding arteries, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were measured before and after acetazolamide administration. VS was higher in patients with SCD compared to controls (p. |
Impact of PET-CT status on progression-free survival for relapsed follicular lymphoma patients undergoing autologous stem cell transplant. Superior progression-free survival was observed in 115 (67%) patients obtaining CMR versus 57 (33%) non-CMR patients (3-year PFS 50% vs 22%, p=0.011) and by Deauville score pre-autoSCT (continuous variable 1-5, hazard ratio (HR) 1.32, p=0.049). PETstatus was independently associated with PFS (non-CMR HR 2.02, p=0.003), overall survival (non-CMR HR 3.08, p=0.010) and risk for relapse (non-CMR HR 1.64, p=0.046) post autoSCT by multivariable analysis. Our data suggests PET-status pre-autoSCT provides clear prognostic value and may help improve patient selection for autoSCT. |
Interplay between hypertriglyceridemia and acute promyelocytic leukemia mediated by the cooperation of peroxisome proliferator-activated receptor alpha with the PML/RAR alpha fusion protein on super-enhancers. PPARa knockdown affected the expression of target genes responsible for APL proliferation, including FLT3, and functionally inhibited the proliferation of APL cells. Moreover, in vivo results in mice having high-fat diet-induced high triglyceride levels supported the connection between high triglyceride levels and the leukemic burden, as well as the involvement of PPARa-mediated-FLT3 activation in the proliferation of APL cells. Our findings shed light on the association between APL proliferation and high triglyceride levels and provide a genetic link to PPARa-mediated hyperlipidemia in APL. |
Meis1 supports leukemogenesis through stimulation of ribosomal biogenesis and Myc. This was accompanied by an elevated resistance against inhibition of rRNA synthesis and translation, but without affecting steady-state protein synthesis. Finally, we demonstrate that HoxA9 and Meis1 proteins are stabilized by post-translational modification. Mutation of HoxA9/Meis1 phosphorylation sites or inhibition of casein kinase 2 lead to rapid protein degradation suggesting a potential pathway for pharmacological intervention. |
| J Hematol Oncol |
Incidence, mortality, risk factors, and trends for Hodgkin lymphoma: a global data analysis. There was an increasing trend in Hodgkin lymphoma incidence, especially among subjects who were female, younger population, and from Asian countries. Further studies are needed to investigate the reasons for these epidemiologic trends. |
Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations. Our analysis represents one of the largest cohorts of EM AML and establishes key molecular markers linked to EM, providing new evidence that EM is associated with adverse risk in AML and may warrant allogeneic HCT in eligible patients with EM. |
Safety of two-dose COVID-19 vaccination (BNT162b2 and CoronaVac) in adults with cancer: a territory-wide cohort study. Neither vaccine was associated with a higher risk of AESI for patients with active cancer (BNT162b2: HR 0.30, 95% CI 0.08-1.09; CoronaVac: 0.14, 95% CI 0.02-1.18) or patients with history of cancer (BNT162b2: 0.62, 95% CI 0.30-1.28; CoronaVac: 0.45, 95% CI 0.21-1.00). In this territory-wide cohort study of patients with cancer, the incidence of AESI following vaccination with two doses of either BNT162b2 or CoronaVac vaccines was low. The findings of this study can reassure clinicians and patients with cancer about the overall safety of BNT162b2 and CoronaVac in patients with cancer, which could increase the COVID-19 vaccination rate in this vulnerable group of patients. |
| Lancet Haematol |
Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial. Interpretation Elotuzumab plus lenalidomide and dexamethasone did not significantly improve progression-free survival versus lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for HSCT. Although these data contribute to the treatment landscape, further research is needed to find ways to improve treatments in the front-line setting. Funding Bristol Myers Squibb. |
Addition of navitoclax to ongoing ruxolitinib treatment in patients with myelofibrosis (REFINE): a post-hoc analysis of molecular biomarkers in a phase 2 study. Interpretation These biomarker analyses reveal clinically meaningful splenic responses independent of high molecular risk mutation status in patients treated with navitoclax plus ruxolitinib who were not benefiting from ruxolitinib monotherapy. Furthermore, the overall survival benefit observed in those with an improvement in fibrosis or a reduction in variant allele frequency is suggestive of disease modification, implying the therapeutic potential of adding navitoclax to ruxolitinib for patients with myelofibrosis who had disease progression or suboptimal response to ruxolitinib monotherapy. Funding AbbVie. |
| Leukemia |
Changing causes of death in persons with haematological cancers 1975-2016. Non-cancer death was the major cause of death in persons with chronic lymphocytic leukaemia, Hodgkin lymphoma and chronic myeloid leukaemia, mostly from cardio-vascular diseases. The greatest relative decrease in index-cancer deaths was amongst persons with Hodgkin lymphoma, chronic myeloid leukaemia and chronic lymphocytic leukaemia, where the proportion of non-cancer deaths increased substantially. Changing distribution of causes of death across haematological cancers reflects substantial progress in some cancers and suggests strategies to improve the survival of persons with haematological cancers in the future. |
Co-variates associated with outcomes of tyrosine kinase-inhibitor therapy in persons with chronic myeloid leukaemia initially presenting in accelerated phase. Based on number of adverse prognostic co-variates of TFS and survival, respectively, subjects were classified into the low- (none), intermediate- (one) and high-risk (=2) cohorts with significant difference in TFS and survival (all p |
Idelalisib activates AKT via increased recruitment of PI3Kd/PI3Kß to BCR signalosome while reducing PDK1 in post-therapy CLL cells. We detected similar, patient-specific recruitment pattern of PI3K-isoforms by BCAP/CD19 in post-idelalisib CLL cells with increased AKT-activation. Interestingly, a stronger inhibitory effect of idelalisib on P-AKT (T308) than S473 was discernible in idelalisib-treated cells despite increased recruitment of PI3Kd/PI3Kß and accumulation of phosphatidylinositol-3,4,5-triphosphate; which could be attributed to reduced PDK1 activity. Thus, administration of isoform-specific inhibitors may prove more effective strategy for treating CLL patients. |
Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life. |
Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia. T-ALLs co-expressing mutant IL7R and Myc activate STAT5 and AKT pathways, harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T-ALLs expressing Myc alone. Moreover, limiting-dilution cell transplantation experiments reveal that activated IL-7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T-ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential. |
Pediatric T-ALL type-1 and type-2 relapses develop along distinct pathways of clonal evolution. T-ALLs that later progressed to type-2 relapses exhibited a complex subclonal architecture, unexpectedly, already at the time of initial diagnosis. Deconvolution analysis of ATAC-Seq profiles showed that T-ALLs later developing into type-1 relapses resembled a predominant immature thymic T-cell population, whereas T-ALLs developing into type-2 relapses resembled a mixture of normal T-cell precursors. In sum, our analyses revealed fundamentally different mechanisms driving either type-1 or type-2 T-ALL relapse and indicate that differential capacities of disease evolution are already inherent to the molecular setup of the initial leukemia. |
PU.1 and MYC transcriptional network defines synergistic drug responses to KIT and LSD1 inhibition in acute myeloid leukemia. Using a live cell biosensor for AKT activity, we identify early adaptive changes in kinase signaling following KIT inhibition that are reversed with the addition of LSD1 inhibitor via modulation of the GSK3a/b axis. Multi-omic analyses, including scRNA-seq, ATAC-seq and CUT&Tag, confirm these mechanisms in primary KIT-mutant AML. Collectively, this work provides rational for a clinical trial to assess the efficacy of KIT and LSD1 inhibition in patients with KIT-mutant AML. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
A CRISPR View of Hematopoietic Stem Cells: Moving Innovative Bioengineering into the Clinic. In this review, we discuss recent achievements in CRISPR-mediated genomic engineering and how these new tools have advanced the understanding of HSC heterogeneity and function throughout life. Additionally, we highlight how these techniques can be used to answer previously inaccessible questions and the challenges to implement them. Finally, we focus on their translational potential to both model and treat hematological diseases in the clinic. |
Assessment of donor cell engraftment after hematopoietic stem cell transplantation for sickle cell disease: A review of current and future methods. Direct measures of RBC chimerism exist but are not routinely used. In this review, we critically examine the current methodologies for assessing donor engraftment, highlight the limitations of these different methods and present emerging and novel technologies with the potential to improve clinical monitoring of RBC engraftment post-HSCT for SCD. Promising alternative methodologies include RBC-specific flow cytometry, RBC-specific RNA analysis, and quantification of plasma cell-free DNA derived specifically from nucleated RBCs. |
| Ann Oncol |
| Blood |
| CA Cancer J Clin |
Navigating financial toxicity in patients with cancer: A multidisciplinary management approach. The case presentations in this report provide a practical context to summarize authors' recommendations for patient-level FT management, supported by a review of key supporting evidence and a discussion of challenges to mitigating FT in oncology care. CA Cancer J Clin. 2022;72:000-000. |
| J Hematol Oncol |
Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets. Thus, targeting these immunosuppressive cells and the related signals is the promising therapy to improve the efficacy of immunotherapies and reverse the immune resistance. However, even with certain success in preclinical studies or in some specific types of cancer, large perspectives are unknown for these immunosuppressive cells, and the related therapies have undesirable outcomes for clinical patients. In this review, we comprehensively summarized the phenotype, function, and potential therapeutic targets of these immunosuppressive cells in the tumor microenvironment. |
Single-cell sequencing: a promising approach for uncovering the mechanisms of tumor metastasis. SCS is also used to identify therapeutic targets related to metastasis as it provides insights into the distribution of tumor cell subsets and gene expression differences between primary and metastatic tumors. Additionally, SCS techniques in combination with artificial intelligence (AI) are used in liquid biopsy to identify circulating tumor cells (CTCs), thereby providing a novel strategy for treating tumor metastasis. In this review, we summarize the potential applications of SCS in the field of tumor metastasis and discuss the prospects and limitations of SCS to provide a theoretical basis for finding therapeutic targets and mechanisms of metastasis. |
The potential role of N7-methylguanosine (m7G) in cancer. Increasing evidence indicates a critical role for m7G in human disease development, especially cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. Currently, the underlying molecular mechanisms of m7G modification in cancer are not comprehensively understood. Here, we review the current knowledge regarding the potential function of m7G modifications in cancer and discuss future m7G-related diagnostic and therapeutic strategies. |
Tumor organoids: applications in cancer modeling and potentials in precision medicine. Additionally, vascularization and immune microenvironment modeling based on organoid technology will also be described. Furthermore, we will summarize the great potential of tumor organoids in predicting the therapeutic response, investigating resistance-related mechanisms, optimizing treatment strategies, and exploring potential therapies. In addition, the bottlenecks and challenges of current tumoroids will also be discussed in this review. |
Worked to the bone: antibody-based conditioning as the future of transplant biology. Most antibody-based conditioning therapies involve monoclonal/naked antibodies, such as alemtuzumab for graft-versus-host disease prophylaxis and rituximab for Epstein-Barr virus prophylaxis, which are both in Phase II trials for inclusion in conditioning regimens. Nevertheless, alternative immune-based therapies, including antibody-drug conjugates, radio-labelled antibodies and CAR-T cells, are showing promise in a conditioning setting. Here, we analyse the current status of antibody-based drugs in pre-transplant conditioning regimens and assess their potential in the future of transplant biology. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Cancer J |
| J Hematol Oncol |
Homologous recombination deficiency (HRD) can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients. We reported for the first time the association between HRD event and enhanced neoadjuvant immunotherapy response in lung cancer. The power of HRD event in patient therapeutic stratification persisted in multifaceted public cohorts. We propose that HR pathway gene status could serve as novel and additional indicators guiding immune-neoadjuvant and immunotherapy treatment decisions for NSCLC patients. |
Post-transplant cyclophosphamide alters immune signatures and leads to impaired T cell reconstitution in allogeneic hematopoietic stem cell transplant. Importantly, upregulation of PD-1 on CD8 T cells was persistent through day 180 and these T cells were less functional, manifested by reduced cytokine production upon anti-CD3/CD28 stimulation. Furthermore, we found a significant correlation of T cell immune phenotypes to clinical outcome (disease relapse and GVHD) in patients who received PTCy. Our novel findings provide critical information to understand the mechanism of how PTCy impacts immune reconstitution in allo-HSCT and may subsequently lead to optimization of our clinical practice using this treatment. |
| Leukemia |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Lancet Haematol |
| Leukemia |